rs279665

chr7-122105911-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005763.4(AASS):c.1279-4231T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,060 control chromosomes in the GnomAD database, including 1,138 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1138 hom., cov: 32)
• Consequence: AASS NM_005763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

Genes affected

AASS (HGNC:17366): (aminoadipate-semialdehyde synthase) This gene encodes a bifunctional enzyme that catalyzes the first two steps in the mammalian lysine degradation pathway. The N-terminal and the C-terminal portions of this enzyme contain lysine-ketoglutarate reductase and saccharopine dehydrogenase activity, respectively, resulting in the conversion of lysine to alpha-aminoadipic semialdehyde. Mutations in this gene are associated with familial hyperlysinemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AASS	NM_005763.4	c.1279-4231T>G		intron_variant		ENST00000417368.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AASS	ENST00000417368.7	c.1279-4231T>G		intron_variant		1	NM_005763.4	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15630 AN: 151942 Hom.: 1119 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.0572

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0822

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0744

Gnomad OTH AF: 0.0991

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 15708 AN: 152060 Hom.: 1138 Cov.: 32 AF XY: 0.0997 AC XY: 7413 AN XY: 74372

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.0596

Gnomad4 ASJ AF: 0.0572

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0826

Gnomad4 FIN AF: 0.0496

Gnomad4 NFE AF: 0.0745

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0924 Hom.: 98

Bravo AF: 0.107

Asia WGS AF: 0.0770 AC: 268 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	4.4
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs279665; hg19: chr7-121745965;